Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI).

METHODS:

A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations.

RESULTS:

Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient.

CONCLUSION:

Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

• Authors: S Salloway, S Ferris, A Kluger, R Goldman, T Griesing, D Kumar, S Richardson, Donepezil 401 Study Group
• Journal: Neurology (Neurology) Vol. 63 Issue 4 Pg. 651-7 (Aug 24 2004) ISSN: 1526-632X [Electronic] United States
• PMID: 15326237 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cholinesterase Inhibitors
• Indans
• Nootropic Agents
• Piperidines
• Donepezil

Topics

• Aged
• Aged, 80 and over
• Cholinesterase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Cognition Disorders (drug therapy)
• Donepezil
• Double-Blind Method
• Female
• Humans
• Indans (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Neuropsychological Tests
• Nootropic Agents (administration & dosage, adverse effects, therapeutic use)
• Piperidines (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome